What question did this study set out to answer?

To evaluate the clinical relevance of TNF-α and MAdCAM-1 in pediatric pouchitis.

February 19, 2026Scientific Reports0 citationsOpen Access

Therapeutic targets established in adult ulcerative colitis exhibit correlations with disease severity and pathological relevance in pediatric pouchitis

SOSayaka OtakeGunma University EKEnkhtuvshin KhorolgaravGunma University TYTakehiko YokoboriGunma University

Key Points

To evaluate the clinical relevance of TNF-α and MAdCAM-1 in pediatric pouchitis.
Performed immunohistochemical analysis of ileal and pouch biopsy tissues from pediatric patients with UC.
Quantitatively assessed expression of TNF-α, MAdCAM-1, and immune markers (CD68, CD163) using HALO image analysis.
Collected paired pouchitis biopsies during active and improved disease phases.
Increased MAdCAM-1-positive vasculature and CD68-positive cell infiltration in pouchitis specimens.
MAdCAM-1 and TNF-α expression reduced in low-PDAI tissues from paired samples.
Expression of MAdCAM-1 and TNF-α positively correlated with inflammatory cell infiltration.

Abstract

Pediatric pouchitis has no established treatment strategy, and management is particularly challenging in recurrent or antibiotic-refractory cases. Tumor necrosis factor alpha (TNF-α) and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) are established and emerging therapeutic targets, respectively, in adult ulcerative colitis (UC) and pouchitis; however, their expression profiles and clinical relevance in pediatric pouchitis remain unclear. Therefore, we evaluated the pathological and clinical significance of TNF-α and MAdCAM-1 in pediatric pouchitis. We performed immunohistochemical analysis of surgically resected ileal tissues and subsequent pouch biopsy specimens obtained from 10 pediatric patients with UC. Paired pouchitis biopsies were collected during both active (high pouchitis disease activity index, PDAI) and improved (low PDAI) phases. TNF-α, MAdCAM-1, and immune cell markers (CD68, CD163, and CD8) in the mucosal stroma were quantitatively assessed using HALO image analysis. Compared with baseline ileal tissues, pouchitis specimens showed increased MAdCAM-1-positive vasculature and infiltration of CD68- and CD163-positive cells. In paired specimens, MAdCAM-1, TNF-α, and CD68 expression was significantly reduced in low-PDAI tissues. MAdCAM-1 and TNF-α expression was positively correlated with inflammatory cell infiltration. This exploratory study provided the first histological evidence that MAdCAM-1 and TNF-α could be upregulated in pediatric pouchitis and associated with disease severity, highlighting the pathological relevance of adult UC therapeutic targets in this setting.

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